Along with its outstanding
antidepressant effect, electroconvulsive shock (ECS) can induce learning and memory impairment.
Propofol and
ketamine have shown to be useful in alleviating the learning and memory impairment. Nevertheless, the mechanism still remains unclear. This study investigated the role of
NMDA receptor (NMDAR)-mediated metaplasticity in the learning and memory impairment induced by ECS, as well as the
neuroprotective effect of
propofol and
ketamine in depressive rats. Rats received ECS or ECS under
anesthetics after chronic unpredictable mild stress procedure. Long-term potentiation (LTP) was tested by extracellular recording. LTD/LTP threshold was assessed by stimulation of different frequencies. Additionally, NMDAR-mediated field excitatory postsynaptic potential (fEPSP) and NMDAR input/output relationship were detected under hippocampal slice perfusion. Results showed that
propofol or low-dose
ketamine could partially alleviate ECS-induced LTP impairment, while
propofol combined with low-dose
ketamine almost reversed the LTP impairment. LTP under ECS was increased by stronger stimulation. ECS could up-regulated LTD/LTP threshold, while
propofol or
ketamine could down-regulate it. Moreover, ECS activated NMDAR, while
propofol and
ketamine could inhibit the activation of NMDAR. NMDAR input/output relationship decrease was induced by preconditioning (an analog of ECS in hippocampal slice), however, NMDAR input/output relationship increased by
propofol or
ketamine. In conclusion, ECS-induced
cognitive impairment is caused by NMDAR-mediated metaplasticity via up-regulation of LTD/LTP threshold.
Propofol or
ketamine alleviates the
cognitive impairment, possibly by down-regulating the threshold via inhibition of NMDAR activation induced by ECS.